Given the potential role of NO and the ROS's in physiopathology, the new derivatives described corresponding to general formula (I) may produce beneficial or favourable effects in the treatment of pathologies where these chemical species are involved. In particular:                Proliferative and inflammatory diseases such as for example atherosclerosis, pulmonary hypertension, respiratory distress, glomerulonephritis, portal hypertension, psoriasis, arthrosis and rheumatoid arthritis, fibroses, angiogenesis, amyloidoses, inflammations of the gastrointestinal system (ulcerative or non ulcerative colitis, Crohn's disease), diarrhea.        Diseases affecting the pulmonary system or airways (asthma, sinusitis, rhinitis).        Cardio-vascular and cerebro-vascular disorders including for example, migraine, arterial hypertension, septic shock, ischemic or hemorragic cardiac or cerebral infarctions, ischemia and thromboses;        Disorders of the central or peripheral nervous system such as for example neurodegenerative diseases where there can in particular be mentioned cerebral infarctions, sub-arachnoid hemorrhaging, aging, senile dementia including Alzheimer's disease, Huntington's chorea, Parkinson's disease, Creutzfeld Jacob disease and prion diseases, amyotrophic lateral sclerosis; ocular neuropathies such as glaucoma but also pain, cerebral and bone marrow traumas, addiction to opiates, alcohol and addictive substances, cognitive disorders, encephaldpathies, and encephalopathies of viral or toxic origin;        Disorders of the skeletal muscle and neuromuscular joints (myopathy, myosis) as well as cutaneous diseases.        Cataracts.        Organ transplants.        Autoimmune and viral diseases such as for example lupus, AIDS, parasitic and viral infections, diabetes, and multiple sclerosis.        Cancer.        Neurological diseases associated with intoxication (Cadmium poisoning, inhalation of n-hexane, pesticides, herbicides), associated with treatments (radiotherapy) or disorders of genetic origin (Wilson's disease).        All the pathologies characterized by an excessive production or dysfunction of NO and/or ROS's.        
In all these pathologies, there is experimental evidence demonstrating the involvement of NO or ROS's (J. Med. Chem. (1995) 38, 4343-4362; Free Radic. Biol. Med. (1996) 20, 675-705; The Neuroscientist (1997) 3, 327-333).
Moreover, in earlier patents, the inventors already described NO Synthase inhibitors and their use (U.S. Pat. No. 5,081,148; U.S. Pat. No. 5,360,925), and more recently the combination of these inhibitors with products possessing antioxidant or antiradicular properties (patent application PCT WO 98/09653). In applications not yet published, they also described other derivatives of amidines or, more recently, derivatives of aminopyridines. These derivatives of amidines or aminopyridines have the characteristic of being both inhibitors of NO Synthases and inhibitors of ROS.
A subject of Application WO 95/05363 is compounds which are inhibitors of NO synthases of general formula (A1)
in which    D represents phenyl, pyridinyl or an aromatic heterocycle with 5 members containing 1 to 4 heteroatoms chosen form O, N and S, these three groups being optionally substituted by one or more groups chosen from (C1-C6)alkyl, (C1-C6)alkoxy, halogen, (C1-C6)perfluoralkyl, or D represents, (C1-C6)perfluoroalkyl;    R1 represents hydrogen, (C1-C6)alkyl or halogen;    R2 represents —X(CH2)nZCONR3R4, —X(CH2)nNHCO(CH2)sNR3R4, —X(CH2)PNR3R4, —X(CH2)nNHCOR5 OR (CH2)qNHC(NH)R6,    R3 and R4 independently represent hydrogen, (C1-C6)alkyl, —(CH2)rA, —(CH2)mOA or —CH(CH3)(CH2)tA;    or the NR3R4 group represents 1-indanyl, piperonylamino, piperidynyl, morpholinyl, pyrrolidinyl, 1,2,3,4-tetrahydroisoquinolinyl or piperazinyl optionally substituted in position 4 by (C1-C6)alkyl;    R5 represents (C1-C6)alkyl, (C1-C6)perfluoroalkyl, —(CH2)r—A or —O(CH2)wA;    A represents phenyl, pyridinyl, pyrimidinyl or an aromatic heterocycle with 5 members containing 1 to 4 heteroatoms chosen form O, N and S, these 4 groups being optionally substituted by one or more groups chosen from (C1-C6)alkyl, halogen, nitro, cyano and trifluoromethyl;    R6 represents phenyl, pyridinyl or an aromatic heterocycle with 5 members containing 1 to 4 heteroatoms chosen form O, N and S, these three groups being optionally substituted by one or more groups chosen from (C1-C6)alkyl, (C1-C6)alkoxy, halogen, (C1-C6)perfluoralkyl, or R6 represents (C1-C6)perfluoroalkyl;    n and r independently represent integers from 0 to 6;    p and w independently represent integers from 1 to 5;    m represents an integer from 2 to 5;    q and t independently represent integers from 0 to 5;    s represents an integer from 1 to 3;    X represents O or a bond;    Z represents O, NR7 or a bond;    R7 represents hydrogen or (C1-C6)alkyl;    it being understood that:            (a) D, when it contains a heteroatom, is not connected to the remainder of the compound of formula (A1) by the heteroatom;        (b) when R2 represents —X(CH2)nZCONR3R4 and neither X nor Z represents a bond then n represents an integer from 2 to 6;        (c) when R2 represents —X(CH2)nNHCO(CH2)sNR3R4 or a —X(CH2)nNHCOR5 and X represents O, then n represents an integer from 2 to 6;        (d) when R2 represents —X(CH2)pNR3R4 and X represents O, then p represents an integer from 2 to 5;        (e) when R2 represents —(CH2)qNHC(NH)R6, R1 represents hydrogen, D represents phenyl and R6 represents phenyl, then q does not represent 0;        (f) when R2 represents —(CH2)qNHC(NH)R6, R1 represents hydrogen, D and R6 represent 2-chlorophenyl, then q does not represent 0;        (g) when R2 represents —(CH2)qNHC(NH)R6, R1 represents hydrogen, D and R6 represent 3-pyridinyl, then q does not represent 0; and        (h) when R2 represents —(CH2)qNHC(NH)R6, R1 represents hydrogen, D and R6 represent 4-pyridinyl, then q does not represent 0.        
A subject of the patent application PCT WO 98/42696 is compounds which are inhibitors of NO synthases and ROS traps of general formula (A2)
in which    A represents one of the
radicals in which R1 and R2 represent, independently, a hydrogen atom, a halogen, the OH group, a linear or branched alkyl or alkoxy radical having 1 to 6 carbon atoms, R3 represents a hydrogen atom, a linear or branched alkyl radical having 1 to 6 carbon atoms or a —COR4 radical,    R4 represents a linear or branched alkyl radical having 1 to 6 carbon atoms, and R5 represents a hydrogen atom, the OH group or a linear or branched alkyl or alkoxy radical having 1 to 6 carbon atoms;    B represents a linear or branched alkyl radical having 1 to 6 carbon atoms, carbocyclic or heterocyclic aryl with 5 or 6 members containing from 1 to 4 heteroatoms chosen from O, S, N and in particular the thiophene, furan, pyrrole or thiazole radicals, the aryl radical being optionally substituted by one or more groups chosen from the linear or branched alkyl, alkenyl or alkoxy radicals having 1 to 6 carbon atoms,    X represents —Z1, —Z1—CO—, —CH═CH—CO—, —Z1—NR3—CO═, —Z1—NR3—CS—, —Z1NR3—SO2— or a single bond;    Y represents a radical chosen from the —Z2-Q, piperazine, homopiperazine, 2-methylpiperazine, 2,5 dimethylpiperazine, 4-aminopiperidine, —NR3—Z2-Q-, —NR3—CO—Z2-Q-, —NR3—NH—CO—Z2—, —NH—NH—Z2—, —NR3—O—Z2—, —NR3—SO2—NR3—Z2, —O—Z2-Q-, —O—CO—Z2-Q or —S—Z2-Q-radicals,    in which Q represents a single bond, O—Z3, R3N—Z3 or S—Z3;    Z1, Z2 and Z3 independently represent a single bond or a linear or branched alkylene radical having 1 to 6 carbon atoms,    and R6 represents a hydrogen atom or the OH group.